This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 2-Methoxyestradiol (2-ME2) is a natural product of the estrogen, estradiol. Recent laboratory studies suggest that 2-ME2 is an effective cancer therapy, decreasing growth and causing cancer cell death in multiple types of cancer. Because of these encouraging results in the laboratory, 2-ME2 was given orally (capsule form) in clinical trials involving patients with solid tumors, breast cancer and prostate cancer. One of the consistent objectives in all three studies included measuring 2-ME2 blood levels. Generally, 2-ME2 was noted to be well-tolerated with only limited side effects. However, in the majority of the patients, blood levels of 2-ME2 were low suggesting that the drug was not getting absorbed by the stomach and/or was being quickly destroyed by the liver and, therefore, was not adequately reaching the cancer in amounts to be effective. To address this problem, in our study we have proposed two specific aims. In specific aim 1, we will design new a formulation (change in the chemical structure) of 2-ME2 which will not be immediately inactivated within the body, and, therefore, will be better able to reach the cancer target. In specific aim 2, using a cancer mouse animal model system we will examine the blood levels and effectiveness of the new 2-ME2 and we will compare these results to the unaltered 2-ME2. If successful, the results of these studies would most definitively act as a forerunner to design new clinical trials with this new formulation and help identify a new treatment against a wide array of cancers.